16-3299360-C-G

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033208.4(TIGD7):c.1255G>C(p.Asp419His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000484 in 1,587,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00051 ( 0 hom. )

Consequence

TIGD7
NM_033208.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.186

Variant links:

Genes affected

TIGD7 (HGNC:18331): (tigger transposable element derived 7) The protein encoded by this gene belongs to the tigger subfamily of the pogo superfamily of DNA-mediated transposons in humans. These proteins are related to DNA transposons found in fungi and nematodes, and more distantly to the Tc1 and mariner transposases. They are also very similar to the major mammalian centromere protein B. The exact function of this gene is not known. [provided by RefSeq, Jul 2008]

TIGD7 links:

ZNF263 (HGNC:13056): (zinc finger protein 263) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and transcription cis-regulatory region binding activity. Involved in negative regulation of transcription by RNA polymerase II and positive regulation of transcription by RNA polymerase II. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF263 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10367715).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIGD7	NM_033208.4 link	c.1255G>C	p.Asp419His	missense_variant	Exon 2 of 2	ENST00000396862.2	NP_149985.2	Q6NT04-1
ZNF263	NM_001411015.1 link	c.*46+204C>G		intron_variant	Intron 7 of 7		NP_001397944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TIGD7	ENST00000396862.2 link	c.1255G>C	p.Asp419His	missense_variant	Exon 2 of 2	2	NM_033208.4	ENSP00000380071.1	Q6NT04-1
ZNF263	ENST00000575332.2 link	c.*250C>G		3_prime_UTR_variant	Exon 7 of 7	3		ENSP00000461146.2	D3DUC1
ZNF263	ENST00000574674.2 link	c.*46+204C>G		intron_variant	Intron 7 of 7	2		ENSP00000461755.2	D3DUC1

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000182

AC:

AN:

230786

Hom.:

AF XY:

0.000200

AC XY:

AN XY:

125236

show subpopulations

Gnomad AFR exome

AF:

0.0000659

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000380

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000508

AC:

729

AN:

1435482

Hom.:

Cov.:

AF XY:

0.000452

AC XY:

322

AN XY:

712588

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000643

Gnomad4 OTH exome

AF:

0.000372

GnomAD4 genome

AF:

0.000263

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000500

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000381

Hom.:

Bravo

AF:

0.000230

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000132

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 01, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1255G>C (p.D419H) alteration is located in exon 2 (coding exon 1) of the TIGD7 gene. This alteration results from a G to C substitution at nucleotide position 1255, causing the aspartic acid (D) at amino acid position 419 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.057

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.55

M_CAP

Benign

0.0043

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.4

REVEL

Benign

0.18

Sift

Benign

0.12

Sift4G

Uncertain

0.011

Polyphen

1.0

Vest4

0.15

MVP

0.19

MPC

0.21

ClinPred

0.082

GERP RS

2.5

Varity_R

0.058

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over